A number of drugs including chloroquine, triparanol, chlorophenteramine and 4,4' diethylaminoethoxyhexestrol have been found to produce a generalized accumulation of phospholipids in the tissues of animals and man. The latter drug caused a significant outbreak of human "acquired phospholipidosis" and foam cell syndrome in Japan; the other agents cause phospholipidosis in animals (rats). In addition to causing a general increase in the tissue content of all phospholipids, these drugs cause striking increases (10 to 40 fold) in the level of bis(monoacylglyceryl) phosphate (BMP). The mechanism of these drug actions is currently unknown, but the major hypotheses are that the drugs inhibit: 1) Phospholipid catabolism by phospholipases; 2) phosphatidate phosphohydrolase conversion of phosphatidic acid to 1,2 diacylglycerol (and lecithin) with resultant increased synthesis of acidic phospholipids. This project proposes comprehensive in vivo and in vitro studies using rats to elucidate the effect of these drugs on the biosynthesis, catabolism, and turnover of phospholipids, and specifically bis(monoacylglyceryl) phosphate, to elucidate the mechanisms of this disorder. The lipid storage bodies which accumulate in the tissues will be isolated and characterized, and their contribution to the process assessed by biochemical, physiological and morphologic techniques. Electron microscopic studies will be done to find the progression of changes induced by the drugs on the liver ultrastructure. Drugs in current human use which have similar structures will be screened to see if they have the tendency to produce phospholipid accumulation using a unique urine sediment lipid analysis technique.